Feline herpesvirus 1 (FHV-1) is a member of the subfamily Alphaherpesvirinae and consists of a single linear molecule of double-stranded DNA (Rota et al., 1986). FHV-1 is wide-spread in the feline population, with as many as 71% of cats seropositive for this virus (Lappin et al., 2002), and it causes 50% of the cases of upper respiratory disease in cats (Maggs et al., 1999). Of these infections, FHV-1 causes the most severe clinical disease (Povey, 1976). Acute infections are usually localized to the respiratory tract, and clinical signs include pyrexia, ocular and nasal discharge, rhinitis, tracheitis, and depression (Burgener et al., 1988; Love, 1971). Primary ocular infection, as occurs in humans with the related herpes simplex virus type 1, consistently produces conjunctivitis and minimal corneal involvement. Acute signs, though potentially severe, usually resolve in a few weeks (Povey, 1976).
FHV-1 is very fragile in nature and does not survive long outside the host, so transmission requires close contact, especially mucosal contact; sneezing and short distance, droplet spread are significant in transmission in large confined populations, such as in breeding colonies and rescue catteries (Murphy et al., 1999). Upper respiratory infections in cats is second only to overcrowding as the leading cause of euthanasia in shelters, and FHV-1 is one of the main causes of shelter respiratory disease (Bannasch et al., 2005).
FHV-1 has been perpetuated in nature as a result of its ability to produce latent infections, and latently infected cats represent the most important reservoir of the virus (Gaskell et al., 1977; Maggs et al., 2003). Approximately 80% of cats infected with the virus become latently infected (Gaskell et al., 1977). During periods of stress such as changes in housing, parturition and lactation, or with corticosteroid administration, recrudescence occurs with associated viral shedding, with or without clinical disease. Also, 29% of latently infected cats are spontaneous shedders (Gaskell et al., 1977). Though the majority of latently infected cats do not develop chronic clinical disease (Andrew, 2001), there is still a large percentage of adult cats that have this problem (Stiles, 2003). The clinical manifestations of disease due to repeated recrudescence, including corneal ulcerations (Bistner et al., 1971), eosinophilic keratitis, or corneal sequestration (Nasisse et al., 1998), are significant and can lead to blindness (Andrew, 2001).
Antiviral medications approved for treatment of herpes simplex virus type 1 in humans are only minimally effective for treatment of these chronic cases in cats (Stiles, 1995). This is possibly due in part to the need for frequent application of the virostatic drugs and poor owner compliance (Stiles, 1995). Vaccines are available for FHV-1, but because the virus is poorly immunogenic (August, 1984), the vaccines do not prevent infection or shedding and only produce partial protection from clinical disease (Bittle et al., 1975). Therefore, development of a new therapeutic for FHV-1 would be beneficial.
Recently, a mechanism called RNA interference (RNAi) has been manipulated for prevention of various mammalian viral infections both in vitro and in vivo (Kim et al., 2007). RNA interference is a double stranded, RNA-guided gene silencing pathway that is found in a variety of eukaryotic organisms, including yeast, plants, and mammals (for a review, see reference Hammond, 2005). The double stranded RNA, small interfering RNAs (siRNA), that triggers the pathway can be supplied exogenously to silence specific genes (Elbashir et al., 2001; Hammond, 2005).